Ekaterina Osipova, Meng‐Ching Ko, Konstantin M. Petricek, Simon Yung Wa Sin, Thomas F. Brown, Sylke Winkler, Martin Pippel, Julia Jarrells, Susanne Weiche, Mai‐Britt Mosbech, Fanny Taborsak-Lines, Chuan Wang, Orlando Contreras-Lopez, Remi‐André Olsen, Philip Ewels, Daniel Mendez-Aranda, Andrea H. Gaede, Keren R. Sadanandan, Gabriel W. Low, Amanda Monte, Ninon Ballerstädt, Nicolas M. Adreani, Lucía Mentesana, Auguste M. P. von Bayern, Alejandro Rico‐Guevara, Scott V. Edwards, Carolina Frankl‐Vilches, Heiner Kuhl, Antje Bakker, Manfred C. Gahr, Douglas L. Altshuler, William A. Buttemer, Michael Schupp, Maude W. Baldwin, Michael Hiller, Timothy B. Sackton
High-sugar diets cause human metabolic diseases, yet several bird lineages convergently adapted to feeding on sugar-rich nectar or fruits. We investigated the underlying molecular mechanisms in hummingbirds, parrots, honeyeaters, and sunbirds by generating nine new genomes and 90 tissue-specific transcriptomes. Comparative screens revealed an excess of repeated selection in both protein-coding and regulatory sequences in sugar-feeding birds, suggesting reuse of genetic elements. Sequence or expression changes in sugar-feeders affect genes involved in blood pressure regulation and lipid, amino acid, and carbohydrate metabolism, with experiments showing functional changes in honeyeater hexokinase 3. MLXIPL , a key regulator of sugar and lipid homeostasis, showed convergent sequence and regulatory changes across all sugar-feeding clades; experiments revealed enhanced sugar-induced transcriptional activity of hummingbird MLXIPL , highlighting its adaptive role in high-sugar diets.